Couching of cataractous lens in microphthalmic eyes with irido-fundal coloboma: revisiting the historical technique.

PURPOSE: Cataract surgery in microphthalmic eyes is challenging due to anatomical restraints, hard bulky nucleus. This series aims to evaluate the safety and efficacy of couching of intraocular lens in irido-fundal coloboma with microphthalmos. SETTING: Tertiary care centre in South India. DESIGN: Retrospective non-comparative study in eyes with irido-fundal coloboma, corneal diameter < 7 mm and brown cataract. Visual acuity less than 6/60 in other eye. METHODS: Anterior chamber entry made, zonules broken and lens dislocated into the vitreous cavity in a controlled manner. Baseline Clinico-demographic details, corrected distance visual acuity (CDVA), Intra-ocular pressure (IOP), corneal diameter, axial length, lens status and post-surgery CDVA, IOP and complications recorded and followed up for atleast 6 months. RESULTS: Fifteen eyes of 15 subjects were evaluated with a mean age 49.4 ± 10.9 years. At baseline, mean IOP 14.5 ± 3.8 mmHg, mean axial length 19.3 ± 0.5 mm, mean corneal diameter was 6.5 ± 0.34 mm and CDVA 2 logMAR which improved to 1.5 logMAR at 3 months (p value 0.002). Transient spike in IOP in 33.3% subjects was medically managed with no significant difference in IOP (p > 0.05) at baseline (14.5 ± 3.8 mmHg), 3 months post-surgery (16 ± 2.8 mmHg) and 6 months post-surgery (14.9 ± 2.5 mmHg). One patient underwent re-couching. No other major complications were noted. CONCLUSION: Couching of cataractous lens is an effective and safe method in microphthalmic eyes with irido-fundal coloboma as last resort procedure, where no other surgical procedure may work. It provides an ambulatory gain of visual acuity in previously non-ambulatory subjects. Corneal measurements help in determining the subset of patients where couching offers viable option.

Development of a potent embryonic chick lens model for studying congenital cataracts in vivo.

Congenital cataracts are associated with gene mutations, yet the underlying mechanism remains largely unknown. Here we reported an embryonic chick lens model that closely recapitulates the process of cataract formation. We adopted dominant-negative site mutations that cause congenital cataracts, connexin, Cx50E48K, aquaporin 0, AQP0R33C, αA-crystallin, CRYAA R12C and R54C. The recombinant retroviruses containing these mutants were microinjected into the occlusive lumen of chick lenses at early embryonic development. Cx50E48K expression developed cataracts associated with disorganized nuclei and enlarged extracellular spaces. Expression of AQP0R33C resulted in cortical cataracts, enlarged extracellular spaces and distorted fiber cell organization. αA crystallin mutations distorted lens light transmission and increased crystalline protein aggregation. Together, retroviral expression of congenital mutant genes in embryonic chick lenses closely mimics characteristics of human congenital cataracts. This model will provide an effective, reliable in vivo system to investigate the development and underlying mechanism of cataracts and other genetic diseases.

Atypical presentation of peripheral posterior lenticonus and role of multi-modal ocular imaging in its diagnosis and management.

A 6-year-old systemically healthy child presented with visual acuity of 1/60, N18 oculusdextrus (OD), and 6/18, N6 oculus sinister (OS). Slit-lamp biomicroscopy revealed suspicious bilateral inferotemporal pigmented ciliary body (CB) tumour, protruding posterior capsule and temporal posterior subcapsular cataract oculus uterque. Anterior segment optical coherence tomography, ultrasonography, ultrasonic biomicroscopy and Scheimpflug imaging revealed protruding posterior capsule and cortex abutting but not arising from CB suggestive of peripheral pigmented posterior lenticonus with hypermetropia (axial length 20.27 mm OD and 19.97 mm OS). Aberrometry revealed high internal aberrations and low Dysfunctional Lens Index (DLI). Lens aspiration with intraocular lens implantation in the bag OD and contact lens correction OS were undertaken. The child had a postoperative visual gain of 3/60, N18 with improved aberrometric profile OD, and was advised amblyopia therapy. Rarely posterior lenticonus can mimic a CB mass. Multi-modal ocular imaging can aid in its diagnosis and management. DLI may serve as a useful indicator of surgery in such cases.

Rapamycin relieves the cataract caused by ablation of Gja8b through stimulating autophagy in zebrafish.

Macroautophagy/autophagy is known to be important for intracellular quality control in the lens. GJA8 is a major gap junction protein in vertebrate lenses. Mutations in GJA8 cause cataracts in humans. The well-known cataractogenesis mechanism is that mutated GJA8 leads to abnormal assembly of gap junctions, resulting in defects in intercellular communication among lens cells. In this study, we observed that ablation of Gja8b (a homolog of mammalian GJA8) in zebrafish led to severe defects in organelle degradation, an important cause of cataractogenesis in developing lens. The role of autophagy in organelle degradation in lens remains disputable. Intriguingly, we also observed that ablation of Gja8b induced deficient autophagy in the lens. More importantly, in vivo treatment of zebrafish with rapamycin, an autophagy activator that inhibits MAPK/JNK and MTORC1 signaling, stimulated autophagy in the lens and relieved the defects in organelle degradation, resulting in the mitigation of cataracts in gja8b mutant zebrafish. Conversely, inhibition of autophagy by treatment with the chemical reagent 3-MA blocked these recovery effects, suggesting the important roles of autophagy in organelle degradation in the lens in gja8b mutant zebrafish. Further studies in HLE cells revealed that GJA8 interacted with ATG proteins. Overexpression of GJA8 stimulated autophagy in HLE cells. These data suggest an unrecognized cataractogenesis mechanism caused by ablation of Gja8b and a potential treatment for cataracts by stimulating autophagy in the lens.Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; AV: autophagic vacuoles; Dpf: days post fertilization; GJA1: gap junction protein alpha 1; GJA3: gap junction protein alpha 3; GJA8: gap junction protein alpha 8; Hpf: hours post fertilization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; WT: wild type.

Aniridia with lenticular and choroidal coloboma.

This case report presents a rare association of a complete aniridia with lenticular and choroidal coloboma. An 8-year-old female patient was referred to our glaucoma clinic with aniridia, nystagmus and bilateral corneal opacity with right eye being phthisical. Ultrasonography of the phthisical eye revealed the presence of an old closed funnel retinal detachment. Further examination under anaesthesia revealed lens coloboma in the inferonasal quadrant and presence of a choroidal coloboma in the left eye. The intraocular pressure was 28 mmHg with a central corneal thickness of 693 µm. A macula sparing laser barrage around the colobomatous area was done in the left eye and topical ocular hypotensives were started.

Changes in ocular biometry during short-term accommodation in children.

PURPOSE: Near work has been linked with myopia development; however, the underlying mechanism remains unclear. Small increases in axial length during accommodation have previously been reported in adults, and therefore, this study aimed to examine if accommodation-induced changes in ocular biometry also occur in school-aged children. METHODS: A range of ocular biometric measurements were captured during brief accommodation tasks at four demands (0, 3, 6, and 9 D), in a group of 87 non-myopic, school-aged children using a Badal optometer mounted to a non-contact optical biometer (Zeiss IOLMaster 700, https://www.zeiss.com/meditec/int/product-portfolio/optical-biometers/iolmaster-700.html). Reliable biometry measurements and active accommodation were observed for 76 participants who were included in the analysis. The average central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), anterior segment length (ASL), vitreous chamber depth (VCD), and axial length (AL) were determined for each accommodation demand. Raw measurements of AL and VCD were corrected to account for the effect of LT changes during accommodation. RESULTS: On average, AL increased with increasing levels of accommodation (p = 0.005). The mean (SEM, standard error of the mean) AL increase from 0 D to the 3, 6, and 9 D demands was 4 (1), 8 (1), and 15 (2) µm, respectively. All other biometric parameters, except CCT, changed significantly during accommodation. LT and ASL increased, and ACD and VCD decreased significantly with increasing accommodation (all p ≤ 0.02). A longer baseline AL was associated with greater levels of accommodation-induced axial elongation at the 9 D demand (p < 0.0001). CONCLUSIONS: AL increased significantly during accommodation in children, consistent with previous findings in adults up to a 6 D demand. AL continued to increase for higher levels of accommodation (9 D demand), which children may experience during near tasks. These findings provide further insights into potential mechanisms linking near work, axial elongation, and myopia development. However, no myopic children participated in this experiment; therefore, further research is required.

Combination of capsular tension ring and capsular tension segment for the management of lens coloboma >4 clock hours.

Lens colobomas extending more than 4 clock hours and causing visual impairment require lens extraction along with capsular support devices with scleral fixation for adequate centration of the capsular bag and for prevention of capsular fornix aspiration with inadvertent extension of zonular dialysis intraoperatively. In this case series, we describe a technique for the management of isolated lens colobomas involving 4-5 clock hours by clear lens extraction and intraocular lens implantation using a combination of a capsular tension ring with a capsular tension segment (CTS) for the centration and stability of the capsular bag. Hoffman's corneoscleral pocket and half-bow sliding knot technique were used for scleral fixation of the CTS.

Alport syndrome with bilateral simultaneous anterior and posterior lenticonus with severe temporal macular thinning.

Alport syndrome (AS) is a hereditary disease with various modes of inheritance, X-linked being the the most common. Anterior lenticonus is the characteristic abnormality along with perimacular and peripheral fleck retinopathy. Our two cases of AS had simultaneous anterior and posterior lenticonus with severe temporal macular thinning on optical coherence tomography with no specific renal symptomatology and were diagnosed as AS without any invasive renal biopsy. First patient was a 19-year-old man who presented with compound myopia due to bilateral anterior and posterior lenticonus with perimacular fleck retinopathy and lozenge sign and bilateral moderate sensorineural hearing loss (SNHL). Second patient was a 24-year-old man who presented with difficulty in vision due to bilateral anterior and posterior lenticonus with bilateral severe SNHL. Our cases emphasise the crucial role of an ophthalmologist in diagnosing AS before the onset of renal symptoms and prompting further nephrological work-up in the patient or the carrier.

Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway.

Ocular anterior segment dysgenesis (ASD) is a failure of normal development of anterior structures of the eye, leading to lens opacification. The underlying mechanisms relating to ASD are still unclear. Previous studies have implicated transcriptional factor muscle segment homeobox 2 (Msx2) in ASD. In this study, we used Msx2 conditional knockout (CKO) mice as a model and found that Msx2 deficiency in surface ectoderm induced ASD. Loss of Msx2 function specifically affected lens development, while other eye structures were not significantly affected. Multiple lines of evidence show that calcium signaling pathways are involved in this pathogenesis. Our study demonstrates that Msx2 plays an essential role in lens development by activating a yet undetermined calcium signaling pathway.

Loss of ciliary zonule protein hydroxylation and lens stability as a predicted consequence of biallelic ASPH variation.

PURPOSE: Stability of the crystalline lens requires formation of microfibril bundles and their higher-order structures of ciliary zonules. Trauma, malformation, or degeneration of the ciliary zonules can lead to dislocation or displacement of the lens, which in turn can cause transient or permanent loss of visual acuity. The purpose of this study was to identify the predicted substrates of aspartyl/asparaginyl hydroxylase (ASPH), a 2-oxoglutarate- and Fe2+-dependent hydroxylase, which may account for the lens instability phenotype of ASPH-associated syndromes. METHODS: A single proband of European ancestry with spherophakia and high myopia was subjected to exome sequencing. Proteins containing the ASPH hydroxylation motif were identified within the SwissProt protein database. RESULTS: We identified 105 putative substrates of ASPH-mediated hydroxylation in the human proteome, of which two (fibrillin-1 and latent transforming growth factor beta binding protein-2) are associated with inherited ectopia lentis syndromes, and are essential for microfibril and ciliary zonule development. CONCLUSION: Our results implicate ASPH-mediated hydroxylation in the formation of FBN1/LTBP2 microfibril bundles and competent ciliary zonules.

Prevalence of anterior polar cataracts in children and risk factors for amblyopia.

PURPOSE: Anterior polar cataract is an opacity in the anterior capsule of the lens. Anterior polar cataract has historically been considered as a relatively benign condition. The purpose of this study was to estimate the prevalence of anterior polar cataract, to identify the risk factors for amblyopia and to estimate the risk of developing amblyopia in children with anterior polar cataract. METHODS: The medical records for patients with congenital cataracts at the Eye Clinic Rigshospitalet, Rigshospitalet-Glostrup and Kennedy Center covering a ten year period from 2007 to 2016 (both metres  years included) were reviewed. RESULTS: A total of 54 patients with anterior polar cataract were identified. The majority had unilateral anterior polar cataract (72%). Family history of childhood cataracts was frequent (27%) of patients with bilateral anterior polar cataract. There was an overrepresentation of female patients (70%). Amblyopia was found in 55% of the patients. The causes were primarily hypermetropic anisometropia (70%) and astigmatism (52%). Axial length was on average 0.88 mm (SD 0.44) shorter in the eye with anterior polar cataract compared to fellow eyes. CONCLUSION: Anterior polar cataract is a highly amblyogenic condition not because of a visually obstructing lens opacity but because of refractive errors, primarily hypermetropic anisometropia and astigmatism. Anterior polar cataract seems to represent an anomaly in global eye development resulting in reduced axial length. Patients with anterior polar cataract should be monitored to detect and treat amblyopia in time.

Ectopic lens material in an otherwise healthy 5-week-old infant.

PURPOSE: To report the unusual finding of ectopic lens material in an otherwise healthy 5-week-old infant. METHODS: Case report and literature review. RESULTS: An asymptomatic 5-week-old female infant was found to have unilateral ectopic lens material in the retrolental space of the left eye associated with a posterior capsular defect. CONCLUSION: The abnormality is likely embryological in origin, and the established progression for similar conditions means long-term monitoring is required to ensure the best possible visual outcome.

Influence of the vitreolenticular interface in pediatric cataract surgery.

PURPOSE: To report the status of Berger space in pediatric cataract cases and the influence of anterior vitreolenticular interface dysgenesis during primary posterior continuous curvilinear capsulorhexis (PCCC). SETTING: Department of Ophthalmology, Antwerp University Hospital, Edegem, Belgium. DESIGN: Prospective case series. METHODS: The study comprised consecutive pediatric cataract cases planned for bag-in-the-lens intraocular lens (BIL IOL) implantation. A video-based analysis of the surgical interventions included the type of crystalline lens opacification, presence of a posterior capsule plaque (PCP), presence of anterior vitreolenticular interface dysgenesis, complications during primary PCCC, integrity of the anterior hyaloid membrane, need for anterior vitrectomy, and feasibility of BIL IOL implantation. RESULTS: Abnormalities in Berger space were observed in 35 of the 64 pediatric cataract cases. Anterior vitreolenticular interface dysgenesis was most often found in cases with persistent fetal vasculature (PFV) and those with posterior cataract. Anterior vitreolenticular interface dysgenesis was diagnosed significantly more often in eyes with unilateral cataract and those with PCP. In pediatric cataract cases presenting with PCP and anterior vitreolenticular interface dysgenesis, the primary PCCC procedure was surgically more demanding, often resulting in detectable breaks in the anterior hyaloid membrane (58.6%) and sometimes necessitating an unplanned anterior vitrectomy (13.8%). Bag-in-the-lens IOL implantation was feasible in all except 1 eye with PFV, which was left aphakic. CONCLUSIONS: Primary vitreolenticular interface abnormalities are often encountered during pediatric cataract surgeries, especially when confronted with PCP in a unilateral cataract. The presence of anterior vitreolenticular interface dysgenesis may complicate a primary PCCC procedure, resulting in an unplanned anterior vitrectomy in some cases.

Posterior lenticonus with persistent fetal vasculature.

A 10 year old girl present with both eyes central cataract with posterior lenticonus. Intraoperative, she was noted to have both eyes persistent fetal vasculature (PFV). To the best of our knowledge, association of bilateral posterior lenticonus and PFV has not been reported before. This supports the hypothesis that PFV has a role in pathogenesis of posterior lenticonus.